title: N-Phenylpropyl-N'-(3-methoxyphenethyl)piperazine (YZ-185) Attenuates the Conditioned-Rewarding Properties of Cocaine in Mice.
abstract: Sigma receptor antagonists diminish the effects of cocaine in behavioral assays, including conditioned place preference. Previous locomotor activity experiments in mice determined that the sigma receptor ligand YZ-185 (N-phenylpropyl-N'-(3-methoxyphenethyl)piperazine) enhanced cocaine-induced hyperactivity at a lower (0.1  μ mol/kg) dose and dose-dependently attenuated cocaine-induced hyperactivity at higher (3.16-31.6  μ mol/kg) doses. The present study investigated the effect of YZ-185 on cocaine's conditioned-rewarding properties in mice. YZ-185 (0.1, 0.316, 3.16, and 31.6  μ mol/kg) did not have intrinsic activity to produce conditioned place preference or aversion. A higher (31.6  μ mol/kg) YZ-185 dose, but not lower (0.1-3.16  μ mol/kg) YZ-185 doses, prevented the development of place preference to cocaine (66  μ mol/kg). YZ-185 did not alter the expression of cocaine place preference. To further characterize YZ-185's behavioral profile, its effects in the elevated zero maze and rotarod procedures were also determined; YZ-185 produced no significant change from baseline in either assay, indicating that the sigma receptors probed by YZ-185 do not regulate anxiety-like or coordinated motor skill behaviors. Overall, these results suggest that YZ-185 is a sigma receptor antagonist at the 31.6  μ mol/kg dose and demonstrate that sigma receptors can mediate the development of the conditioned-rewarding properties of cocaine.
authors.affiliation: Department of Psychological Sciences, 203 McAlester Hall, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Sage
authors.forename: Scott C
authors.initials: SC
authors.lastname: Vannest
authors.forename: Kuo-Hsien
authors.initials: KH
authors.lastname: Fan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Will
authors.forename: Susan Z
authors.initials: SZ
authors.lastname: Lever
authors.forename: John R
authors.initials: JR
authors.lastname: Lever
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Miller